Bidirectional Hypoxic Extracellular Vesicle Signaling Between Müller Glia and Retinal Pigment Epithelium Regulates Retinal Metabolism and Barrier Function

The retina is highly sensitive to oxygen and blood supply, and hypoxia plays a key role in retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Müller glial cells, essential for retinal homeostasis, respond to injury and hypoxia with reactive gliosis, characterized by upregulation of Glial Fibrillary Acidic Protein (GFAP) and vimentin, cellular hypertrophy, and extracellular matrix changes, which can impair retinal function and repair. The retinal pigment epithelium (RPE) supports photoreceptors, forms part of the blood-retinal barrier, and protects against oxidative stress; its dysfunction contributes to retinal degenerative diseases such as AMD, retinitis pigmentosa (RP), and Stargardt disease (SD).